Factors and outcomes for placental anomalies: An umbrella review of systematic reviews and meta-analyses

Background Placental anomalies, including placenta previa (PP), placenta accreta spectrum disorders (PAS), and vase previa (VP), are associated with several adverse foetal-neonatal and maternal complications. However, there is still a lack of robust evidence on the pathogenesis and adverse outcomes of the diseases. Through this umbrella review, we aimed to systematically review existing meta-analyses exploring the factors and outcomes for pregnancy women with placental anomalies. Methods We searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to February 2023. We used AMSTAR 2 to assess the quality of the reviews and estimated the pooled risk and 95% confidence intervals (CIs) for each meta-analysis. Results We included 34 meta-analyses and extracted 55 factors (27 for PP, 22 for PAS, and 6 for VP) and 16 outcomes (12 for PP, and 4 for VP) to assess their credibility. Seven factors (maternal cocaine use (for PP), uterine leiomyoma (for PP), prior abortion (spontaneous) (PP), threatened miscarriage (PP), maternal obesity (PP), maternal smoking (PAS), male foetus (PAS)) had high epidemiological evidence. Twelve factors and six outcomes had moderate epidemiological evidence. Twenty-two factors and eight outcomes showed significant association, but with weak credibility. Conclusions We found varying levels of evidence for placental anomalies of different factors and outcomes in this umbrella review. Registration PROSPERO: CRD42022300160.


Supplementary file 3: AMSTAR-2 Results
. Q11: If meta-analysis was performed did the review authors use appropriate methods for statistical combination of results?
Q12: If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis?
In the meta-analysis, the authors found women with placenta previa were more likely to have a preterm birth before 37 weeks of gestation (risk difference 0.  25 .

IUGR
In the meta-analysis of over 1593226 singleton pregnancies and 10575 confirmed cases of placenta previa in 13 studies, the authors found that pregnancies with placenta previa were associated with a mild increase in the risk of IUGR, with a pooled OR of 1.19 (95% CI 1.10-1.27) 26.

Other outcomes
In the meta-analysis, the authors sought to evaluate the extent of the association between placenta previa and adverse pregnancy outcomes in singleton gestations 27 .In the comparative studies, placenta previa was significantly associated with lower 1-(RR 3.However, there ws no significantly between placenta previa and SGA (RR 1.01, 95% CI 0.62-1.65;n=5).

Maternal Smoking
Fourteen studies were included in a meta-analysis 28 .Based on the random effect model, the estimated OR of the risk of PAS associated with smoking was 1.21 (95% CI: 1.02, 1.41).Subgroup analysis was conducted based on study design, and the result showed that the association between smoking and PAS among cohort studies was significant 1.35 (95% CI: 1.15, 1.55), but this association among case-control studies was not significant 0.83 (95% CI: 0.47, 1.19).In addition, there was no significant association between smoking and PAS based on crude/adjust form.

HDP
A meta-analysis was performed to evaluate the potential effects of hypertension in pregnancy on the placenta accreta spectrum 29 .The authors found pregnancy-induced hypertension was significantly related to lower prevalence of placenta accreta spectrum (OR 0.56, 95% CI 0.37-0.84;n=6) with moderate heterogeneity compared to pregnant women with no hypertension.When they looked at the result comparing the prevalence of hypertension in pregnancy in women with placenta accreta compared to no placenta accrete, they found that the placenta accreta spectrum was significantly related to lower prevalence of hypertension in pregnancy (OR 0.65, 95% CI 0.43-0.98)with moderate heterogeneity compared to no placenta accrete.

Prior UAE
Three comparator studies that compared the rate of PAS between women who did and did not undergo prior UAE.The unadjusted pooled analysis demonstrated that women with prior UAE had a higher rate of PAS (OR 28.47, 95% CI 7.61-106.57;n=3) than those who did not undergo prior UAE 7 .In the adjusted pooled analysis (all women had PPH during their previous delivery), prior UAE was still associated with PAS (OR 20.82, 95% CI 3.27-132.41;n=2).

ART
The meta-analysis aimed to explore the relation between ART pregnancy and PAS 30 .The authors found the risk of PAS was significantly higher in women who conceived with ART than in those with spontaneous conception (OR 5.03, 95% CI 3.34-7.56;n=9).In the sensitivity analysis accounting for Critically low Q1: Did the research questions and inclusion criteria for the review include the components of PICO?Q2: Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol?Q3: Did the review authors explain their selection of the study designs for inclusion in the review?Q4: Did the review authors use a comprehensive literature search strategy?Q5: Did the review authors perform study selection in duplicate?Q6: Did the review authors perform data extraction in duplicate?Q7: Did the review authors provide a list of excluded studies and justify the exclusions?Q8: Did the review authors describe the included studies in adequate detail?Q9: Did the review authors use a satisfactory technique for assessing the risk of bias (RoB) in individual studies that were included in the review?Q10: Did the review authors report on the sources of funding for the studies included in the review?